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To resolve this, we conditionally deleted\n                  <jats:italic>Ar<\/jats:italic>\n                  in luminal acinar cells\n                  <jats:italic>in vivo<\/jats:italic>\n                  .\n                  <jats:italic>Ar<\/jats:italic>\n                  -deleted luminal cells persisted short-term, in contrast to the rapid regression observed after castration, but were impaired in regeneration and progressively lost. Their depletion was accompanied by replacement through basal-to-luminal differentiation of AR intact basal cells. Transcriptomic and chromatin profiling showed cell-autonomous suppression of the secretory program with induction of stemness, inflammatory, and epithelial-to-mesenchymal transition signatures after AR loss. Mechanistically, the MAP kinase pathway and downstream AP-1 transcription factors were activated and functionally validated, and MAP kinase inhibition selectively depleted AR-deleted luminal cells, indicating a compensatory survival pathway. These findings define intrinsic roles for luminal AR in maintaining differentiation, restraining plasticity, and sustaining regeneration and homeostatic turnover, providing a mechanistic basis for AR dependence in prostate cancer.\n                <\/jats:p>","DOI":"10.64898\/2026.02.13.705807","type":"posted-content","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T03:50:08Z","timestamp":1771300208000},"source":"Crossref","is-referenced-by-count":0,"title":["Cell-Autonomous AR Dependence in Luminal Prostatic Epithelium Governs Survival and Lineage Plasticity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8777-4580","authenticated-orcid":false,"given":"Dan","family":"Li","sequence":"first","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naitao","family":"Wang","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wangxin","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai General Hospital, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jude","family":"Owiredu","sequence":"additional","affiliation":[{"name":"Department of Urology, Weill Cornell Medicine, New York, NY 10065, USA"},{"name":"Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA"},{"name":"Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA"},{"name":"Graduate School of Medical Sciences, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo Hyun","family":"Cho","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana","family":"Schoeps","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shipeng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Shanghai General Hospital, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Multi-Cell Systems, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Un In","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Urology, Weill Cornell Medicine, New York, NY 10065, USA"},{"name":"Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA"},{"name":"Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen Khuan","family":"Wong","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vaishnavi Reeya","family":"Callychurn","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongsu","family":"Wang","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenfei","family":"Kang","sequence":"additional","affiliation":[{"name":"Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Fan","sequence":"additional","affiliation":[{"name":"Molecular Cytology Core Facility, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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